Drug resistance profile and clonality of Plasmodium falciparum parasites in Cape Verde: the 2017 malaria outbreak

Abstract

Background Cape Verde is an archipelago located off the West African coast and is in a pre-elimination phase of malaria control. Since 2010, fewer than 20 Plasmodium falciparum malaria cases have been reported annually, except in 2017, when an outbreak in Praia before the rainy season led to 423 autochthonous cases. It is important to understand the genetic diversity of circulating P. falciparum to inform on drug resistance, potential transmission networks and sources of infection, including parasite importation. Methods Enrolled subjects involved malaria patients admitted to Dr Agostinho Neto Hospital at Praia city, Santiago island, Cape Verde, between July and October 2017. Neighbours and family members of enrolled cases were assessed for the presence of anti-P. falciparum antibodies. Sanger sequencing and real-time PCR was used to identify SNPs in genes associated with drug resistance (e.g., pfdhfr, pfdhps, pfmdr1, pfk13, pfcrt), and whole genome sequencing data were generated to investigate the population structure of P. falciparum parasites. Results The study analysed 190 parasite samples, 187 indigenous and 3 from imported infections. Malaria cases were distributed throughout Praia city. There were no cases of severe malaria and all patients had an adequate clinical and parasitological response after treatment. Anti-P. falciparum antibodies were not detected in the 137 neighbours and family members tested. No mutations were detected in pfdhps. The triple mutation S108N/N51I/C59R in pfdhfr and the chloroquine-resistant CVIET haplotype in the pfcrt gene were detected in almost all samples. Variations in pfk13 were identified in only one sample (R645T, E668K). The haplotype NFD for pfmdr1 was detected in the majority of samples (89.7%). Conclusions Polymorphisms in pfk13 associated with artemisinin-based combination therapy (ACT) tolerance in Southeast Asia were not detected, but the majority of the tested samples carried the pfmdr1 haplotype NFD and anti-malarial-associated mutations in the the pfcrt and pfdhfr genes. The first whole genome sequencing (WGS) was performed for Cape Verdean parasites that showed that the samples cluster together, have a very high level of similarity and are close to other parasites populations from West Africa.

Malaria diagnostic methods with the elimination goal in view

“…However, the Island still records a few cases of indigenous infections and imported cases, mostly originating from neighboring African countries. The country aimed at eliminating malaria by 2020 but experienced an epidemic in 2017 however; its last local case was in January 2018 (DePina et al 2020 ; Da Veiga Leal et al 2021 ) and has currently applied for malaria elimination status (WHO 2021a , b , c ). As part of its strategic plan to attain elimination, the country ensured that quality-assured diagnoses were done in all health facilities and, as such become the main source of passives cases following, which confirmed cases are reported within 24 h and hospitalized for treatment (WHO 2021a , b , c ).…”

Evidence of a Recent Bottleneck in Plasmodium falciparum Populations on the Honduran–Nicaraguan Border

“…The genetic diversity of Plasmodium spp. has been related to the ability of parasites to adapt adequately to their hosts through the selection of advantageous traits, such as antigenic variability that allows them to evade the immune response, as well as the emergence of mutations responsible for resistance to antimalarials [3][4][5][6][7]. Genetically diverse populations of Plasmodium are common in regions with high transmission patterns, such as sub-Saharan Africa and some Southeast Asian countries [8][9][10][11][12], but as the incidence of malaria declines, the parasite's genetic diversity is expected to decline as well [13,14].…”

Factors Associated With Resistance to In-Hospital Treatment of Malaria in Angolan Patients

“…Our data is similar to data from the study carried out in Cape Verde, which showed that of the 131 patients and 137 close contacts followed, malaria was predominantly alone (73.3%), in male (65.6%), and younger than cases not associated with malaria ( P < .001), students and tertiary sector activities accounted for 80.2% of malaria cases and multiple logistic regression models suggested an increased risk of malaria because of gender male (OR = 4.99; 95% CI 2.90-8.58) and single (OR = 1.92, 95% CI 1.02-3.58), with potential risk in older age (OR = 0.98; 95%CI 0.97-1.00). 17 …”

“…Our data is similar to data from the study carried out in Cape Verde, which showed that of the 131 patients and 137 close contacts followed, malaria was predominantly alone (73.3%), in male (65.6%), and younger than cases not associated with malaria (P < .001), students and tertiary sector activities accounted for 80.2% of malaria cases and multiple logistic regression models suggested an increased risk of malaria because of gender male (OR = 4.99; 95% CI 2.90-8.58) and single (OR = 1.92, 95% CI 1.02-3.58), with potential risk in older age (OR = 0.98; 95%CI 0.97-1.00). 17 When evaluating how pharmacological procedures were related to resistance to malaria treatment, it was observed that although almost all patients received antimalarial treatment, especially Artemether, that the use of certain drugs from other groups, with antibiotics, antipyretics, and others, when combined with antimalarial treatment, may increase or reduce the possibility of resistance (Table 2). Our data do not show associations between artemether-lumefantrine and artesunateamodiaquine, which seems to be more effective drugs due to their mechanism of action and therefore have been proposed as alternatives in the treatment of parasites drug-resistant.…”